Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-1119. doi: 10.1097/CHI.0b013e3181b76658.
To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.
Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed.
At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p < .05). All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8. Discontinuation rates due to adverse events were as follows: placebo 7.7%, aripiprazole 5 mg/day 9.4%, 10 mg/day 13.6%, and 15 mg/day 7.4%. The most common adverse event leading to discontinuation was sedation. There were two serious adverse events: presyncope (5 mg/day) and aggression (10 mg/day). At week 8, mean weight change (last observation carried forward) was as follows: placebo +0.3 kg, aripiprazole 5 mg/day +1.3 kg, 10 mg/day +1.3 kg, and 15 mg/day +1.5 kg; all p < .05 versus placebo.
Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder.
评估阿立哌唑治疗孤独症谱系障碍儿童和青少年激惹的短期疗效和安全性。
这项为期 8 周的双盲、随机、安慰剂对照、平行分组研究，共纳入了 218 例（年龄 6-17 岁）孤独症谱系障碍患儿和青少年，这些患儿存在易激惹、攻击、自伤行为或上述症状组合，按 1:1:1:1 的比例随机分为阿立哌唑（5、10 或 15mg/天）或安慰剂组。采用照顾者评定的异常行为检查表激惹分量表（主要疗效指标）和临床医生评定的临床总体印象-改善评分评估疗效。还评估了安全性和耐受性。
在第 8 周时，所有阿立哌唑剂量组的异常行为检查表激惹分量表评分的平均改善均显著优于安慰剂组（5mg/天，-12.4；10mg/天，-13.2；15mg/天，-14.4；安慰剂组，-8.4；均 P<.05）。在第 8 周时，所有阿立哌唑剂量组的临床总体印象-改善评分的平均改善均显著优于安慰剂组。因不良事件而停药的发生率如下：安慰剂组为 7.7%，阿立哌唑 5mg/天组为 9.4%，10mg/天组为 13.6%，15mg/天组为 7.4%。导致停药的最常见不良事件是镇静。有 2 例严重不良事件：晕厥前兆（5mg/天）和攻击（10mg/天）。第 8 周时，体重变化的平均值（最后一次观测结转）如下：安慰剂组+0.3kg，阿立哌唑 5mg/天组+1.3kg，10mg/天组+1.3kg，15mg/天组+1.5kg；均 P<.05，与安慰剂组相比。
阿立哌唑治疗孤独症谱系障碍相关激惹患儿和青少年有效，且通常安全、耐受良好。
